Usefulness of Plasma Brain Natriuretic Peptide Levels in Predicting Dobutamine-Induced Myocardial Ischemia Junko Asada, MD, Hisako Tsuji, MD, Toshiji Iwasaka, MD, James D. Thomas, MD, and Michael S. Lauer, MD Plasma brain natriuretic peptide (BNP) levels have been associated with left ventricular dysfunction and acute myocardial infarction. Although natriuretic peptide re- sponses have been linked to exercise-induced myocar- dial ischemia, it is not known whether BNP levels predict dobutamine-induced myocardial ischemia. The aim of this study was to determine whether elevations in BNP levels immediately before or after dobutamine-induced stress are associated with echocardiographic myocar- dial ischemia. Plasma BNP was measured before and after stress during dobutamine-stress echocardiography in 317 patients (aged 68  11 years; 46% women) who had creatinine <1.5 mg/dl and did not have valvular disease. Ischemia, as assessed by blinded echocardio- graphic interpretation, was noted in 31 patients (10%). In univariable analyses, prestress BNP was predictive of echocardiographic ischemia (rates of ischemia accord- ing to tertiles of BNP 4%, 9%, and 16%, chi-square for trend  8, p  0.0059). The change in BNP levels with dobutamine stress was not associated with ischemia. In multivariable analyses, after adjusting for age, gender, and left ventricular ejection fraction, BNP before and after stress remained predictive of ischemia (1 SD in- crease in the log of resting BNP adjusted odds ratio 2.0, 95% confidence interval 1.3 to 3.0, p  0.002). In this pilot study, resting BNP was predictive of dobutamine- induced ischemia. Future work is needed to confirm these findings. 2004 by Excerpta Medica, Inc. (Am J Cardiol 2004;93:702–704) A lthough dobutamine stress echocardiography is useful for detecting myocardial ischemia, 1 it re- quires specialized equipment and skilled personnel. Brain natriuretic peptide (BNP) is a neurohormone synthesized in and secreted from ventricular myocar- dium in response to volume expansion and pressure overload, 2,3 which may be induced by myocardial ischemia. 4 Therefore, plasma BNP levels could pre- dict stress-induced ischemia. We assessed the value of plasma BNP immediately before and after dobut- amine-induced stress as a correlate of echocardio- graphic myocardial ischemia. METHODS Study sample: Consecutive patients with known or suspected coronary artery disease referred for dobut- amine echocardiography at the Cleveland Clinic Foundation were eligible. The institutional review board in the Cleveland Clinic Foundation approved the study, and written informed consent was obtained from all enrolled patients. Exclusions were refusal, resting systolic blood pressure 180 mm Hg, serum creatinine 1.5 mg/dl, severe valvular disease, and previous enrollment in this study. Dobutamine echocardiography: Patients underwent dobutamine echocardiography according to standard procedures. 1 Briefly, after obtaining resting images, do- butamine infusion was begun at 5 g/kg/min and titrated upward every 3 minutes until a maximum dose was achieved. Atropine was administered if the test was negative at a dobutamine dose of 40 g/kg/min and heart rate was 85% of the maximal predicted rate, unless the patient had glaucoma or benign prostate hypertrophy. Handgrip was also used at peak dose. Parasternal long- and short-axes and apical 4- and 2-chamber views were acquired at each stage of stress. Echocardiographic readings were blinded to BNP lev- els and clinical characteristics. Left ventricular (LV) ejection fraction was measured off-line in a core lab- oratory using the modified Simpson’s rule. Ischemia was defined as the occurrence of new wall motion abnormalities developing during stress. Scar was con- sidered present when wall motion abnormalities seen at rest remained unchanged during stress. Measurement of plasma BNP levels: After at 5 minutes of supine rest, 6 ml of whole blood was drawn, mixed with aprotinine, immediately placed in ice, and centrifuged. Plasma was extracted and was stored at -80°C. Immediately after conclusion of the dobutamine study (1 minute), the dobutamine line was flushed with normal saline solution. After withdrawing and discarding 10 ml of blood with a separate syringe, 6 ml of whole blood was drawn and same procedures were repeated. From the Cardiovascular Center, Kansai Medical University, Morigu- chi, Japan; Health Examination Center of Moriguchi-City, Moriguchi, Japan; and Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio. This study was supported by a grant from the Promotion and Mutual Aid Corporation for Private Schools of Japan, Tokyo, Japan. Manuscript received July 2, 2003; revised manuscript received and accepted November 18, 2003. Address for reprints: Hisako Tsuji, MD, Health Examination Center of Moriguchi-City, 1–13–7, Ohmiya-Dori, Moriguchi-City, Osaka, Japan 570-0033. E-mail: tsuji@takii.kmu.ac.jp. 702 ©2004 by Excerpta Medica, Inc. All rights reserved. 0002-9149/04/$–see front matter The American Journal of Cardiology Vol. 93 March 15, 2004 doi:10.1016/j.amjcard.2003.11.051